Harsch Devin R, Cox Karin M, Wright Kevin K M, Rice Patrick J, Pasquereau Benjamin, Turner Robert S
Department of Neurobiology, Center for Neuroscience and The Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
Institut des Sciences Cognitives Marc Jeannerod, UMR 5229, Centre National de la Recherche Scientifique, 69675 Bron Cedex, France.
bioRxiv. 2025 Sep 23:2025.09.15.676392. doi: 10.1101/2025.09.15.676392.
How the brain organizes discrete actions into fluid sequences is a central problem in motor neuroscience. Competing models of basal ganglia (BG) function propose that BG neurons either signal sequence boundaries or encode movements across ordinal positions. Prior studies have largely examined fixed sequences with end-of-sequence rewards, leaving open whether such findings generalize to more naturalistic conditions. We trained four rhesus macaques to perform a visuomotor sequence task requiring four or five out-and-back joystick movements to peripheral targets. Sequences were completed under two conditions: a random condition, in which target order varied across trials, and a fixed condition, in which order was predictable and consistent. Rewards were delivered after each movement, dissociating reward timing from sequence completion. We recorded single-unit activity in arm-related regions of the globus pallidus (GP; n = 458) and primary motor cortex (M1; n = 306). Regression analyses revealed that many neurons in both GP and M1 encoded ordinal position within a sequence. Order effects were more frequent in the fixed condition, but were also present during random sequences. We found no evidence for preferential encoding of sequence initiation or termination in overlearned sequences, in contrast to prior studies reporting start/stop signals in basal ganglia. Weak effects appeared under the random condition in one animal pair, but these did not generalize across animals or conditions. Instead, neurons exhibited heterogeneous order-related responses spanning the full sequence. These results demonstrate that GP neurons, like those in M1, encode ordinal position throughout a sequence rather than acting solely as sequence initiators or terminators. This challenges boundary-specific models of BG function and highlights the BG's broader role in representing serial order during motor sequence production.
大脑如何将离散动作组织成流畅序列是运动神经科学中的一个核心问题。关于基底神经节(BG)功能的竞争模型提出,BG神经元要么发出序列边界信号,要么编码跨有序位置的运动。先前的研究大多考察了具有序列末尾奖励的固定序列,尚未明确这些发现是否能推广到更自然的条件下。我们训练了四只恒河猴执行一项视觉运动序列任务,该任务需要进行四到五次往返操纵杆动作,指向周边目标。序列在两种条件下完成:随机条件,即每次试验目标顺序不同;固定条件,即顺序可预测且一致。每次动作后给予奖励,使奖励时间与序列完成相分离。我们记录了苍白球(GP;n = 458)和初级运动皮层(M1;n = 306)与手臂相关区域的单神经元活动。回归分析表明,GP和M1中的许多神经元都编码了序列中的有序位置。在固定条件下,顺序效应更频繁,但在随机序列中也存在。与先前报道基底神经节中有起始/停止信号的研究相反,我们没有发现过度学习序列中优先编码序列起始或终止的证据。在一对动物中,随机条件下出现了微弱效应,但这些效应并未在所有动物或条件下普遍存在。相反,神经元在整个序列中表现出与顺序相关的异质性反应。这些结果表明,GP神经元与M1中的神经元一样,在整个序列中编码有序位置,而不是仅作为序列起始者或终止者发挥作用。这对BG功能的边界特异性模型提出了挑战,并突出了BG在运动序列产生过程中表征序列顺序方面更广泛的作用。